{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T07:31:58Z","timestamp":1772177518099,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>\n                    Chronic consumption of high-fat diets (HFDs) induces obesity and metabolic dysfunction and is accompanied by progressive skeletal muscle wasting. Although aerobic exercise is generally considered less effective for maintaining muscle mass, accumulating evidence suggests that it can attenuate HFD-induced muscle wasting. However, the molecular mechanisms underlying this protective effect remain poorly defined. In this study, we investigated the effects of moderate-intensity continuous training (MICT) on HFD-induced muscle wasting and characterized the associated transcriptomic adaptations in the mouse gastrocnemius muscle. 21 weeks of HFD feeding increased body weight and serum glucose levels and induced marked muscle wasting, as evidenced by reduced gastrocnemius muscle index, impaired forelimb grip strength, decreased muscle fiber cross-sectional area, and excessive intramuscular lipid accumulation. These pathological alterations were significantly attenuated by an 8-week MICT intervention. RNA sequencing revealed that HFD predominantly induced a lipid-centered transcriptional program characterized by enhanced fatty acid uptake, trafficking, and \u03b2-oxidation. In contrast, MICT predominantly suppressed atrophy-associated genes (\n                    <jats:italic>Foxo1<\/jats:italic>\n                    ,\n                    <jats:italic>Fbxo32<\/jats:italic>\n                    , and\n                    <jats:italic>Trim63<\/jats:italic>\n                    ), while exerting minimal effects on myogenic genes (\n                    <jats:italic>Pax7<\/jats:italic>\n                    ,\n                    <jats:italic>Myod1<\/jats:italic>\n                    , and\n                    <jats:italic>Myog<\/jats:italic>\n                    ). Functional enrichment analyses further indicated that MICT modulated signaling pathways related to FoxO, PI3K\u2013Akt, MAPK, and insulin signaling, together with biological processes associated with angiogenesis and calcium signaling. Collectively, these results suggest that MICT mitigates HFD-induced muscle wasting primarily by reprogramming the transcriptome from a lipotoxic, atrophic state toward a more insulin-sensitive, pro-angiogenic profile, with limited myogenic activation.\n                  <\/jats:p>","DOI":"10.3389\/fphys.2026.1796142","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:25:17Z","timestamp":1772169917000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic insights into aerobic exercise-mediated attenuation of high-fat diet\u2013induced muscle wasting"],"prefix":"10.3389","volume":"17","author":[{"given":"Weihao","family":"Hong","sequence":"first","affiliation":[{"name":"School of Physical Education, Quanzhou Normal University","place":["Quanzhou, China"]},{"name":"Division of Sports Science and Physical Education, Tsinghua University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianrong","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, ShanghaiTech University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yisheng","family":"Luan","sequence":"additional","affiliation":[{"name":"Division of Sports Science and Physical Education, Tsinghua University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibin","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Physical Education, Quanzhou Normal University","place":["Quanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueyun","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Physical Education, Quanzhou Normal University","place":["Quanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Sports Science and Physical Education, Tsinghua University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100381","DOI":"10.1016\/j.metop.2025.100381","article-title":"High-fat diet may increase the risk of insulin resistance by inducing dysbiosis","volume":"27","author":"Abbasi","year":"2025","journal-title":"Metabol. Open"},{"key":"B2","doi-asserted-by":"publisher","first-page":"9047821","DOI":"10.1155\/2016\/9047821","article-title":"High fat diet-induced skeletal muscle wasting is decreased by mesenchymal stem cells administration: implications on oxidative stress, ubiquitin proteasome pathway activation, and myonuclear apoptosis","volume":"2016","author":"Abrigo","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0245618","DOI":"10.1371\/journal.pone.0245618","article-title":"Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation","volume":"16","author":"Adhikari","year":"2021","journal-title":"PLoS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1096\/fj.14-255901","article-title":"Acylcarnitines: potential implications for skeletal muscle insulin resistance","volume":"29","author":"Aguer","year":"2015","journal-title":"Faseb J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"455","DOI":"10.3233\/JND-160183","article-title":"Matrix metalloproteinases and tissue inhibitor of metalloproteinases in inflammation and fibrosis of skeletal muscles","volume":"3","author":"Alameddine","year":"2016","journal-title":"J. Neuromuscul. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"105530","DOI":"10.1016\/j.archger.2024.105530","article-title":"Effect of aerobic training versus resistance training for improving cardiorespiratory fitness and body composition in middle-aged to older adults: a systematic review and meta-analysis of randomized controlled trials","volume":"126","author":"An","year":"2024","journal-title":"Arch. Gerontol. Geriatr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1530\/JOE-17-0555","article-title":"Fructose bisphosphatase 2 overexpression increases glucose uptake in skeletal muscle","volume":"237","author":"Bakshi","year":"2018","journal-title":"J. Endocrinol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"775447","DOI":"10.3389\/fimmu.2021.775447","article-title":"\u03b22 integrin CD11d\/CD18: from expression to an emerging role in staged leukocyte migration","volume":"12","author":"Blythe","year":"2021","journal-title":"Front. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"E469","DOI":"10.1152\/ajpendo.00204.2014","article-title":"Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx\/atrogin-1","volume":"307","author":"Bodine","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1038\/ncb1101-1014","article-title":"Akt\/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo","volume":"3","author":"Bodine","year":"2001","journal-title":"Nat. Cell. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"5794","DOI":"10.3390\/cancers14235794","article-title":"Glucose and inositol transporters, SLC5A1 and SLC5A3, in glioblastoma cell migration","volume":"14","author":"Brosch","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e240131","DOI":"10.1530\/ERC-24-0131","article-title":"Mechanisms of RET-mediated signal transduction","volume":"32","author":"Carlomagno","year":"2025","journal-title":"Endocr. Relat. Cancer"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25215079","article-title":"Role of inositols and inositol phosphates in energy metabolism","volume":"25","author":"Chatree","year":"2020","journal-title":"Molecules"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1038\/s12276-023-01019-8","article-title":"TXNIP: a key protein in the cellular stress response pathway and a potential therapeutic target","volume":"55","author":"Choi","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"C1188","DOI":"10.1152\/ajpcell.00485.2025","article-title":"The role of carnitine palmitoyl transferase 2 in the progression of salt-sensitive hypertension","volume":"329","author":"Dissanayake","year":"2025","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s10456-023-09870-z","article-title":"The vascular gene Apold1 is dispensable for normal development but controls angiogenesis under pathological conditions","volume":"26","author":"Fan","year":"2023","journal-title":"Angiogenesis"},{"key":"B17","doi-asserted-by":"publisher","first-page":"7315","DOI":"10.1074\/jbc.RA117.001254","article-title":"Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation","volume":"293","author":"Fazakerley","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1519\/JSC.0000000000003230","article-title":"Resistance training for older adults: position statement from the national strength and conditioning association","volume":"33","author":"Fragala","year":"2019","journal-title":"J. Strength Cond. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.cdtm.2020.06.003","article-title":"High-fat diet-induced adipose tissue expansion occurs prior to insulin resistance in C57BL\/6J mice","volume":"6","author":"He","year":"2020","journal-title":"Chronic Dis. Transl. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"8853541","DOI":"10.1155\/2020\/8853541","article-title":"Myocardin-related transcription factor A (MRTF-A) regulates the balance between adipogenesis and osteogenesis of human adipose stem cells","volume":"2020","author":"Hyv\u00e4ri","year":"2020","journal-title":"Stem Cells Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"C375","DOI":"10.1152\/ajpcell.00379.2020","article-title":"Adipose tissue inflammation and metabolic dysfunction in obesity","volume":"320","author":"Kawai","year":"2021","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/nu8080466","article-title":"Lipid-induced insulin resistance in skeletal muscle: the chase for the culprit goes from total intramuscular fat to lipid intermediates, and finally to species of lipid intermediates","volume":"8","author":"Kitessa","year":"2016","journal-title":"Nutrients"},{"key":"B23","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/BF01076484","article-title":"The function of acyl-coa-binding protein (ACBP)\/Diazepam binding inhibitor (DBI)","volume":"123","author":"Knudsen","year":"1993","journal-title":"Mol. Cell. Biochem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1097\/MNH.0b013e328363ff43","article-title":"Structure, function, and regulation of the SLC4 NBCe1 transporter and its role in causing proximal renal tubular acidosis","volume":"22","author":"Kurtz","year":"2013","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"B25","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s12576-017-0531-2","article-title":"Long-term resistance exercise-induced muscular hypertrophy is associated with autophagy modulation in rats","volume":"68","author":"Kwon","year":"2018","journal-title":"J. Physiol. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/s40520-015-0316-5","article-title":"Effects of chronic high-fat feeding on skeletal muscle mass and function in middle-aged mice","volume":"27","author":"Lee","year":"2015","journal-title":"Aging Clin. Exp. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1161\/CIRCRESAHA.119.315881","article-title":"CITED4 protects against adverse remodeling in response to physiological and pathological stress","volume":"127","author":"Lerchenm\u00fcller","year":"2020","journal-title":"Circ. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.3390\/biomedicines10092283","article-title":"The role of fatty acid binding protein 3 in cardiovascular diseases","volume":"10","author":"Li","year":"2022","journal-title":"Biomedicines"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2561221","DOI":"10.1080\/0886022X.2025.2561221","article-title":"Exercise-mediated amelioration of high-fat diet-induced kidney injury: implications of microRNA regulation","volume":"47","author":"Luan","year":"2025","journal-title":"Ren. Fail"},{"key":"B30","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.cmet.2012.04.010","article-title":"Lipid-induced mitochondrial stress and insulin action in muscle","volume":"15","author":"Muoio","year":"2012","journal-title":"Cell. Metab."},{"key":"B31","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.cytogfr.2015.12.007","article-title":"Common mutations in ALK2\/ACVR1, a multi-faceted receptor, have roles in distinct pediatric musculoskeletal and neural orphan disorders","volume":"27","author":"Pacifici","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186663","article-title":"MuRF1\/TRIM63, master regulator of muscle mass","volume":"21","author":"Peris-Moreno","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.mito.2019.07.009","article-title":"Upregulated PDK4 expression is a sensitive marker of increased fatty acid oxidation","volume":"49","author":"Pettersen","year":"2019","journal-title":"Mitochondrion"},{"key":"B34","doi-asserted-by":"publisher","first-page":"318","DOI":"10.3390\/jcm12010318","article-title":"FAT\/CD36 participation in human skeletal muscle lipid metabolism: a systematic review","volume":"12","author":"Ramos-Jim\u00e9nez","year":"2022","journal-title":"J. Clin. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1016\/j.bbalip.2017.07.009","article-title":"The perilipin family of lipid droplet proteins: gatekeepers of intracellular lipolysis","volume":"1862","author":"Sztalryd","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell. Biol. Lipids"},{"key":"B36","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3390\/biom11040521","article-title":"The mitochondrial carnitine acyl-carnitine carrier (SLC25A20): molecular mechanisms of transport, role in redox sensing and interaction with drugs","volume":"11","author":"Tonazzi","year":"2021","journal-title":"Biomolecules"},{"key":"B37","doi-asserted-by":"publisher","first-page":"C200","DOI":"10.1152\/ajpcell.00334.2025","article-title":"The multifaceted role of MyoD in adult skeletal muscle: homeostasis, regeneration, and diseases","volume":"329","author":"Tsuji","year":"2025","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"16474","DOI":"10.1073\/pnas.1307680110","article-title":"Pax7 is critical for the normal function of satellite cells in adult skeletal muscle","volume":"110","author":"von Maltzahn","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B39","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1007\/s10545-010-9104-8","article-title":"The enzymology of mitochondrial fatty acid beta-oxidation and its application to follow-up analysis of positive neonatal screening results","volume":"33","author":"Wanders","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"12380","DOI":"10.1074\/jbc.RA119.008680","article-title":"Mitochondrial fatty acid oxidation and the electron transport chain comprise a multifunctional mitochondrial protein complex","volume":"294","author":"Wang","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.freeradbiomed.2025.08.043","article-title":"Exercise training ameliorates high-fat diet-induced skeletal muscle atrophy and ferroptosis via downregulation of STING","volume":"240","author":"Xu","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00421-009-1033-6","article-title":"Chronic resistance training decreases MuRF-1 and Atrogin-1 gene expression but does not modify Akt, GSK-3beta and p70S6K levels in rats","volume":"106","author":"Zanchi","year":"2009","journal-title":"Eur. J. Appl. Physiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"19116","DOI":"10.1038\/s41598-021-98771-6","article-title":"Trimetazidine and exercise provide comparable improvements to high fat diet-induced muscle dysfunction through enhancement of mitochondrial quality control","volume":"11","author":"Zhang","year":"2021","journal-title":"Sci. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1007\/s00011-023-01753-9","article-title":"Dual role of ANGPTL4 in inflammation","volume":"72","author":"Zuo","year":"2023","journal-title":"Inflamm. Res."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1796142\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:25:18Z","timestamp":1772169918000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1796142\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":44,"alternative-id":["10.3389\/fphys.2026.1796142"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2026.1796142","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]},"article-number":"1796142"}}